Statin Risk Benefit
Statin medications have recently received adverse publicity regarding the risk of muscle problems including rhabdomyolysis (Click here for Statin Advisory) The risks of these side effects are low and are far outweighed by the proven benefits of this class of medication. Such publicity is unfortunate in that it generates fear and uncertainty, undermines risk reduction strategies and may lead to discontinuation or under-dosing of statin medications. Such a response may result in adverse cardiovascular and cerebrovascular outcomes due to lost benefit. As with all drugs the pros and cons of therapy need to weighed carefully.

The number need to treat (NNT) for statin therapy has been reviewed on the Bandolier EBM website Stain Outcome Trials Update which comments that “across all large outcome studies, irrespective of baseline risk, statins have a NNT of 19 (17-33) for prevention of death or non fatal heart attack or stroke”. A mathematical model has shown that the maximum life years saved occurs if therapy is begun at age 40 in patients at risk. (BMJ Vol 320 22 April 2000: 1134-1140)

The risk of serious myopathy or rhabdomyolysis with use of stains is low:

Drug  Reported Cases of Fatal Rhabdomyolysis
per 1,000,000 US prescriptions since launch 1
Cerivastatin
Lovastatin 
Simvastatin
Pravastatin
Atorvastatin
Fluvastatin
Rosuvastatin		 3.16
0.19
0.12
0.04
0.04
0.00
0.00*

To put risk and benefit in a clearer perspective, for every 100,000 patients treated with a statin in large outcome studies:

Risks: 4 will suffer rhabdomyolysis and 33 will suffer myositis

Benefits:

4S Trial (6 years) [Click Here]

  • prevention of 4,000 deaths
  • prevention of 7,000 nonfatal heart attacks
  • prevention of 6,000 myocardial revascularization procedures

Care (5 years) [Click Here]

  • prevention of 15,000 cardiovascular events in unselected patients
  • prevention of 20,700 cardiovascular events in patients > age 60
  • prevention of 22,800 cardiovascular events in women

Lipid (6.1 Years) [Click Here]

  • prevention of 3,000 deaths
  • prevention of 2,800 non-fatal heart attacks
  • prevention of 900 strokes
  • prevention of 2,300 bypass surgeries
  • prevention of 2,000 angioplasties
  • prevention of 8,200 admissions for unstable angina

HPS (5 years):

  • prevention of 7000-10000 heart attacks, stroke or revascularization

Furthermore, recent trial evidence from PROVE-IT indicates an incremental benefit with high dose versus moderate dose statin in patients with acute coronary syndromes treated over 18-36 months (mean 24 months). This incremental benefit amounts to 3.9 % absolute and 16% relative risk reduction of the primary end-point - a composite of death from any cause, myocardial infarction, documented unstable angina requiring re-hospitalization, revascularization (performed at least 30 days after randomization),and stroke. For 10,000 patients treated this means the prevention of 390 further events.

In summary:

  • The risk of serious muscle problems with statins is low.
  • The benefits of statin therapy significantly outweigh any risk.
  • Higher dosing of statins or use of more a more potent statin provides incremental benefits in high risk patients.
  • Fear of statin adverse effects should not prevent appropriate lipid lowering therapy.

References
1. Staffa JS, Chang J, Green L. Cerivastatin and Reports of Fatal Rhabdomyolysis, N Engl J Med;2002:346(7):539-540.
2. Thompson P, Clarkson P, Karas R.H. Statin-associated  Myopathy. JAMA. 2003;289:1681-1690.
http://jama.ama-assn.org/cgi/content/abstract/289/13/1681
3. Cholesterol and Statin review. Bandolier EBM Website. http://www.jr2.ox.ac.uk/bandolier/Extraforbando/statin.pdf
4. Safety and efficacy of rosuvastatin